As women's smoking rates have caught up with those of men, smoking has emerged as a critical health problem for women. If more specific and effective treatments for women are to be devised, it is important to determine whether previous findings in men can necessarily be generalized to women, or whether biological and/or cultural differences need to be taken into account. Over the past several years, there has been growing recognition that systematic hormonal fluctuations associated with the menstrual cycle have had an impact not only upon reproductive biology but upon numerous other aspects of mood, behavior, and cognitive function. Recent research with women smokers suggests that smoking may be enhanced during menstrual phases associated with physical discomfort and dysphoria and withdrawal symptomatology may be more severe in women who attempt to quit in the latter part of the menstrual cycle. The specific aims of this renewal project are to carry out a sequence of within-subject, repeated measures studies in women smokers over a f-year period: 1) Stress-induction of smoking behavior and nicotine intake across the menstrual cycle, and their relationship to cyclical changes in behavioral, subjective, and physiological variables, will be explored in Study I; nicotine (self- administered via cigarette smoking) serves as the principal dependent variable. 2) Nicotine's acute effects on physiological, behavioral, and subjective responses and on stress hormones (catecholamines and the pro- opiomelanocortin group) will be examined across the menstrual cycle in Studies II and III; nicotine serves as the independent variable and is administered to the smoker in controlled doses via intranasal aerosol. 3) Differences in ability to stop smoking for a week will be tested in two matched groups asked to abstain at different points in the menstrual cycle in Study IV; this study explores the question of whether phase needs to be taken into account in recommendations for smoking cessation. 4) Differences in nicotine intake in the late luteal phase following mid-cycle opioid blockade using naltrexone will be examined in a double-blind, placebo controlled design in Study V, providing a potential explanation for the apparent increase in reinforcement value for smoking in this phase. Because there has been so little systematic research on the behavioral, subjective, physiological, and neurohumoral manifestations of smoking in women, the initial studies will be largely descriptive, with attempts to elucidate mechanisms underlying the dynamic relations between smoking behavior and the menstrual cycle to be undertaken only after a suitable empirical base is established.